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This study aimed to investigate whether there is a systematic change of leg muscle activity, as quantified by surface electromyography (EMG), throughout a standard running footwear assessment protocol at a predetermined running speed.Thirty-one physically active adults (15 females and 16 males) completed 5 testing rounds consisting of overground running trials at a speed of 3.5 m/s. The level of muscle activity from 6 major leg muscles was recorded using surface EMG. The variables assessed were the EMG total intensity as a function of time and the cumulative EMG overall intensity. Systematic effects of the chronological testing round (independent variable) on the normalized EMG overall intensity (dependent variable) were examined using Friedman analysis of variates and post hoc pairwise Wilcoxon signed-rank tests (α = 0.05).There was a systematic reduction in overall EMG intensity for all 6 muscles over the time course of the running protocol (p0.001) until the fourth testing round when EMG intensities reached a steady state. The one exception was the biceps femoris muscle, which showed a significant reduction of EMG intensity during the stance phase (p0.001) but not the swing phase (p = 0.16).While running at a predetermined speed, the neuromuscular system undergoes an adaptation process characterized by a progressive reduction in the activity level of major leg muscles. This process may represent an optimization strategy of the neuromuscular system towards a more energetically efficient running style. Future running protocols should include a familiarization period of at least 7 min or 600 strides of running at the predetermined speed.

This study aimed to investigate if changing the midsole bending stiffness of athletic footwear can affect the onset of lower limb joint work redistribution during a prolonged run.Fifteen trained male runners (10-km time of44 min) performed 10-km runs at 90% of their individual speed at lactate threshold (i.e., when change in lactate exceeded 1 mmol/L during an incremental running test) in a control and stiff shoe condition on 2 occasions. Lower limb joint kinematics and kinetics were measured using a motion capture system and a force-instrumented treadmill. Data were acquired every 500 m.Prolonged running resulted in a redistribution of positive joint work from distal to proximal joints in both shoe conditions. Compared to the beginning of the run, less positive work was performed at the ankle (approximately 9%; p ≤ 0.001) and more positive work was performed at the knee joint (approximately 17%; p ≤ 0.001) at the end of the run. When running in the stiff shoe condition, the onset of joint work redistribution at the ankle and knee joints occurred at a later point during the run.A delayed onset of joint work redistribution in the stiff condition may result in less activated muscle volume, because ankle plantar flexor muscles have shorter muscles fascicles and smaller cross-sectional areas compared to knee extensor muscles. Less active muscle volume could be related to previously reported decreases in metabolic cost when running in stiff footwear. These results contribute to the notion that footwear with increased stiffness likely results in reductions in metabolic cost by delaying joint work redistribution from distal to proximal joints.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

We aimed to examine the effects of a 16-week multimodal exercise program (MEP) on activities of daily living (ADL) in individuals with dementia (IWD). Furthermore, we investigated the participants’ individual response to the MEP and whether baseline cognitive and motor performance explain ADL performance. We conducted a multicenter randomized controlled trial (RCT) involving 319 participants aged ≥ 65 years with mild to moderate dementia. ADL were assessed at baseline and after the 16-week intervention using the Barthel Index (BI), the Erlangen Test of Activities of Daily Living (E-ADL) and the 7‑item Physical Performance Test (PPT-7). We additionally assessed cognitive and motor performance using standardized and validated assessments. Intervention effects were examined through two-factor analysis of variance with repeated measurements applying a per protocol and an intention-to-treat analysis. We compared baseline cognitive and motor performance between positive-responders (positive-R), non-responders (non-R), and negative-responders (negative-R) and examined cognitive and motor performance as potential cofounders of ADL by conducting multiple regression analyses. There were no significant time×group effects on ADL. Between 20 and 32% of participants responded positively to the intervention, i.e., improved ADL performance from baseline to follow-up. Positive-R had worse baseline motor performance compared to non-R. Cognitive and motor performance explained up to 51.4% of variance in ADL. The MEP had no significant overall effect on ADL in IWD. This may be related to insufficient exercise intensity. However, our results indicate that the response to the MEP depends on individual prerequisites which should thus be considered in further research on individual exercise approaches.

In recent editorials of the British Journal of Sports Medicine (Burns & Tam, 2020) and Footwear Science (Frederick, 2020; Hoogkamer, 2020), the effect of midsole construction on running performance...

Increased involvement of the hip musculature during some movements is associated with enhanced performance and reduced injury risk. However, the impact of hip dominant weight training methods on movement strategy has seen limited attention within the literature. The aim of this study was to evaluate if a 9-week hip dominant weight training intervention promotes a more hip dominant movement strategy leading to an improvement in countermovement jump performance. Twenty-two experienced female dancers were recruited and separated into an intervention (age 24.4 ± 6.3 years, body height 165.5 ± 5.8 cm, body mass 65.9 ± 5.6 kg) and a control (age 22.9 ± 5.6 years, body height 163.3 ± 5.4 cm, body mass 57.4 ± 6.8 kg) group. The intervention group participated in a 9-week hip dominant training intervention, which consisted of a wide stance back squat, Romanian deadlift, hip thrusters, and a bent over row. Hip and knee kinematics and kinetics, and countermovement jump performance were assessed pre and post training. Significant interaction effects were found for peak hip joint moment (p = 0.030, η2 = 0.214) and countermovement jump performance (p = 0.003, η2 = 0.356), indicating an increase in peak hip joint moment and countermovement jump performance for the intervention group. Specifically, the intervention group showed a mean increase in jump height of 11.5%. The data show that the use of a hip dominant weight training strategy can improve hip contribution in the propulsion phase of the countermovement jump. Strength and conditioning specialists should incorporate hip dominant weight training exercises to increase hip strength and improve performance.

Suicide in patients with opioid use disorder (OUD) is a complex issue. In addition to accidental intoxications, a higher prevalence of fatal suicides in patients with OUD can be found compared to the general population. In this study, suicides with a diagnosis of OUD documented in the project "Suicides, A National Survey" were extracted from our data bank. Individuals with a diagnosis of OUD in their medical history were compared to other suicides. The analyses included clinical and demographic factors as well as an investigation of suicide methods and toxicology of psychotropic drugs. For the statistical analyses, we applied chi-square tests and calculated odds ratios. Out of 6,495 suicide cases in Switzerland between 2000 and 2010, 215 individuals with a medical history of OUD could be identified. Persons in OUD cases were significantly younger than in other suicide cases (

Objectives Despite difficulties to quantify foot pronation non-invasively and during dynamic tasks, pronation was frequently discussed with respect to injury risk and footwear development. Typically, surrogate measures were used to approximate the movement of pronation showing inconsistent results due to the high variability in the methodology and protocols. This study determines the relationships between all identified pronation variables and aims to reduce the data set to its dominant factors. Design Cross-sectional. Methods Forty barefoot participants (14 F, 26 M) performed four standing tasks (subneutral, bipedal, single-leg with 20° and single-leg with 30° knee flexion), over ground walking (1.5 m/s) and running (3.5 m/s) trials. Manual assessment data, motion capture data, ground reaction forces, and plantar pressure distributions were collected. Sixty-one commonly used pronation measures were compared using Spearman Correlations and a Principal Component Analysis (PCA). Results Two groups of correlated variables were found, 4.2% of them correlated mainly with the longitudinal arch angle (LAA), the other 10.2% correlated with the Achilles tendon angle (β). The remaining 85.6% were not significantly correlated to each other. Conclusions The LAA is representative for the movement of the mid foot and β quantifies rear foot eversion relative to the shank. Since these dominant variables varied independently from each other, both cannot quantify pronation simultaneously. Therefore, it is important to consider and report both, LAA-pronation and β-pronation separately to represent prevalent foot movement properties. Separately assessing the two dominant underlying mechanisms of foot movement may lead to improved guidelines for clinical screening and footwear manufacturing.

Zusammenfassung. Die Betreuung von Demenzkranken hat auf die Angehörigen grosse psychische, physische, soziale, finanzielle und spirituelle Auswirkungen. Stützende und beratende Gespräche können für die Gesundheit des Angehörigen, für die Beziehung zum Demenzkranken sowie zur besseren Behandlung (mittels Shared Decision Making/Behandlungsplanung/Care Planning) des Patienten beitragen. In diesem Artikel wird eine Übersicht über Daten aus der Schweiz und von internationalen Studien gegeben.

Background Attention-deficit/hyperactivity disorder (ADHD) has substantial heritability, and a recent large-scale investigation has identified common genome-wide significant loci associated with increased risk for ADHD. Along the same lines, many studies using noninvasive neuroimaging have identified differences in brain functional connectivity in children with ADHD. We attempted to bridge these studies to identify differences in functional connectivity associated with common genetic risk for ADHD using polygenic risk score (PRS). Methods We computed ADHD PRSs for all participants in our sample (N = 315, children 7–13 years of age, 196 with ADHD and 119 unaffected comparison children) using ADHD data from the Psychiatric Genomics Consortium as a discovery set. Magnetic resonance imaging was used to evaluate resting-state functional connectivity of targeted subcortical structures. Results The functional connectivity between 2 region pairs demonstrated a significant correlation to PRS: right caudate–parietal cortex and nucleus accumbens–occipital cortex. Connectivity between these areas, in addition to being correlated with PRS, was correlated with ADHD status. The connection between the caudate and the parietal region acted as a statistical suppressor, such that when it was included in a path model, the association between PRS and ADHD status was enhanced. Conclusions Our results suggest that functional connectivity to certain subcortical brain regions is directly altered by genetic variants, and certain cortico–subcortical connections may modulate ADHD-related genetic effects.

BackgroundMechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children.MethodsChildren 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577).ResultsADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score.ConclusionCommon genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.

Epigenetic variation in peripheral tissues is being widely studied as a molecular biomarker of complex disease and disease-related exposures. To date, few studies have examined differences in DNA methylation associated with attention-deficit hyperactivity disorder (ADHD). In this study, we profiled genetic and methylomic variation across the genome in saliva samples from children (age 7–12 years) with clinically established ADHD (N = 391) and nonpsychiatric controls (N = 213). We tested for differentially methylated positions (DMPs) associated with both ADHD diagnosis and ADHD polygenic risk score, by using linear regression models including smoking, medication effects, and other potential confounders in our statistical models. Our results support previously reported associations between ADHD and DNA methylation levels at sites annotated to VIPR2, and identify several novel disease-associated DMPs (p SLC7A8 and cg21609804 annotated to MARK2) are also significantly associated with nearby SNPs (p = 1.2e–46 and p = 2.07e–59), providing evidence that disease-associated DMPs are under genetic control. We also report a genome-wide significant association between ADHD polygenic risk and variable DNA methylation at a site annotated to the promoter of GART and SON (p = 6.71E–8). Finally, we show that ADHD-associated SNPs colocalize with SNPs associated with methylation levels in saliva. This is the first large-scale study of DNA methylation in children with ADHD. Our results represent novel epigenetic biomarkers for ADHD that may be useful for patient stratification, reinforce the importance of genetic effects on DNA methylation, and provide plausible molecular mechanisms for ADHD risk variants.

Background The emergence and spread of multidrug-resistant organisms (MDROs) represent a threat to human and animal health. Objectives To assess duration of carriage of MDROs in dogs and cats presented to veterinary clinics/hospitals in Switzerland. To estimate prevalence, duration of and risk factors for MDRO carriage in their owners and the occurrence of co-carriage in owner-pet pairs. Methods Prospective, longitudinal, observational study. Nasal swabs and fecal samples were collected from 50 owners of dogs and cats presented to 3 large veterinary hospitals, 1 medium-sized clinic and 1 practice. If pet or owner tested positive for a MDRO, follow-up samples were collected for up to 8��months. Methicillin-resistant (MR) Staphylococcus aureus, MR S. pseudintermedius, MR coagulase-negative staphylococci (MRCoNS), MR Macrococcus spp., cephalosporinase- and carbapenemase-producing (CP) Enterobacterales were isolated and further characterized by MALDI-TOF MS, microdilution, ��-lactam resistance gene detection, REP/ERIC-PCR, multilocus sequence typing or whole-genome sequencing. Risk factors for MDRO carriage in owners were explored based on questionnaire-derived data. Results Five out of 50 owners carried 3rd generation cephalosporin-resistant Enterobacterales (3GC-R-Ent.), and 5/50 MRCoNS. In 3 dogs and 4 cats carriage of 3GC-R-Ent. persisted for up to 136��days after discharge (median 99��days, IQR 83��days, range 36-136��days), in two cats isolates were carbapenem-resistant. Owner-pet co-carriage was not observed. No specific risk factors for MDRO carriage in owners were identified. Conclusions After discharge from veterinary care, dogs and cats may carry 3GC-R-Ent. for prolonged time periods. Carriage of MDROs was common in owners, but pet-owner co-carriage of the same MDRO was not observed.

BackgroundThe clinical utility of MRI neuroimaging studies of psychopathology has been limited by a constellation of factors—small sample sizes, small effect sizes, and heterogeneity of methods and samples across studies—that hinder generalizability and specific replication. An analogy is early genomics studies of complex traits, wherein a move to large, multi-site samples and a focus on cumulative effects (polygenic scores) led to reproducible and clinically applicable effects from genome-wide association studies. A similar logic in MRI may provide a way to improve reproducibility, precision, and clinical utility for brain-wide MRI association studies.MethodsPolyneuro scores (PNS) represent the cumulative effect of brain-wide measures—in the present case, resting-state functional connectivity (rs-fcMRI) associated with ADHD symptoms. These scores were constructed and validated using baseline data from the Adolescent Brain Cognitive Development (ABCD, N=5666) study, with a reproducible matched subset as the discovery cohort (N=2801). Association between the PNS and ADHD symptoms was further tested in an independent case-control cohort, the Oregon-ADHD-1000 (N=533).ResultsThe ADHD PNS was significantly associated with ADHD symptoms in both the ABCD and Oregon cohorts after accounting for relevant covariates (p-values < 0.001). While the strongest effects contributing to the PNS were concentrated among connections involving the default mode and cingulo-opercular networks, the most predictive PNS involved connectivity across all brain networks. These findings were robust to stringent motion thresholds. In the longitudinal Oregon-ADHD-1000, non-ADHD comparison youth had significantly lower ADHD PNS (β=-0.309, p=0.00142) than children with persistent ADHD (met diagnostic criteria at two or more time points from age 7 to 19). The ADHD PNS, however, did not reliably mediate polygenic risk for ADHD. Instead, the PNS and an ADHD polygenic score were independently associated with ADHD symptoms.ConclusionsA polyneuro risk score representing cumulative ADHD-associated resting-state connectivity was robustly associated with ADHD symptoms in two independent cohorts using distinct sampling designs, yet was independent of polygenic liability for ADHD, suggesting the need to examine environmental influences. The polyneuro score approach holds promise for improving the reproducibility of neuroimaging studies, identifying their clinical utility, and unraveling the complex relationships between brain connectivity and the etiology of behavioral disorders.

Sustainable tourism builds on the Sustainable Development Goals (SDGs), involving the consideration of people with disabilities, which necessitates their corresponding integration within tourism development. The noteworthy potential of accessible tourism is demonstrated in several studies. Hence, efforts have already been made to develop and adapt products in this regard. However, there are still challenges related to the inclusion of people with disabilities in tourism. Therefore, this study examines product development for accessible tourism through four case studies that have developed and implemented products for people with disabilities in the past. Data is gathered by means of qualitative interviews with managers of these product developments, and data is also triangulated with secondary information. The results show that product development for people with disabilities strongly depends on the immediate collaboration of all stakeholder groups and the inclusion of people with disabilities, building on the underlying values of the destination. Furthermore, the study indicates that in accordance with the Triple Bottom Line (TBL), sustainable product developments for accessible tourism are based on the sustainable tourism principles. Thus, both theoretical and practical implications for tourism facilities as well as for destination management organizations can be derived.

Human movement patterns were shown to be as unique to individuals as their fingerprints. However, some movement characteristics are more important than other characteristics for machine learning algorithms to distinguish between individuals. Here, we explored the idea that movement patterns contain unique characteristics that differentiate between individuals and generic characteristics that do not differentiate between individuals. Layer-wise relevance propagation was applied to an artificial neural network that was trained to recognize 20 male triathletes based on their respective movement patterns to derive characteristics of high/low importance for human recognition. The similarity between movement patterns that were defined exclusively through characteristics of high/low importance was then evaluated for all participants in a pairwise fashion. We found that movement patterns of triathletes overlapped minimally when they were defined by variables that were very important for a neural network to distinguish between individuals. The movement patterns overlapped substantially when defined through less important characteristics. We concluded that the unique movement characteristics of elite runners were predominantly sagittal plane movements of the spine and lower extremities during mid-stance and mid-swing, while the generic movement characteristics were sagittal plane movements of the spine during early and late stance.

Customized insoles are commonly prescribed to prevent or treat a variety of foot pathologies and to reduce foot and lower limb fatigue. Due to the patient-specific design and production of such orthotics, the concept of self-selected customized orthotics (SSCO) has recently been developed. The goal of this study was to assess the impact of SSCO technology on several physiological and biomechanical variables during uphill power walking. Thirty male participants underwent an uphill power walking intervention at constant speed in two insoles conditions (control and SSCO). The electromyographic (EMG) activity of their right gastrocnemii and vastii muscles was measured. Perceived fatigue was assessed every 5 minutes and the intervention stopped when the targeted fatigue level was reached. Baseline and post-intervention assessments were also performed. Sixty-three percent of the participants experienced an improvement in foot fatigue while wearing the SSCO. The foot arch seemed to collapse less when participants wore the SSCO, but statistical significance was not reached. The changes in mean EMG activity was not consistent between the 50% isometric contraction and the walking trial. In conclusion, while some interesting trends were observed when wearing SSCO, further investigations should be performed to try and reach statistical significance.

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Different factors were shown to alter the vibration characteristics of soft-tissue compartments during running. Changing pre-heel strike muscle activation or changing footwear conditions represents two possibilities to influence the vibration response via frequency shift or altered damping. Associated with the study of muscle pre-tuning is the difficulty in quantifying clean experimental data for the acceleration of soft-tissue compartments and muscle activities in heterogeneous populations. The purpose of this study was to determine the vibration and pre-tuning response to footwear across a wide range of participants during running and establish and describe groups formed according to the damping coefficient. 32 subjects were used for further analysis. The subjects ran at a self-selected speed (5 min) on a treadmill in two different shoes (soft & hard), while soft-tissue accelerations and muscle activation at the gastrocnemius medialis were quantified. Damping coefficients, total muscle intensity and dominant vibration frequencies were determined. Anthropometrics and skinfold measurements of the lower limbs were obtained. According to the damping coefficient response to the footwear intervention, three groups were formed, with most runners (n = 20) showing less damping in the hard shoe. Total muscle intensity, anthropometrics, and dominant vibration frequency across footwear were not different for these three groups. Most runners (84.4%) used the strategy of adjusting the damping coefficients significantly when switching footwear. Despite damping being the preferred adjustment to changes in footwear, muscle pre-tuning might not be the only mechanism to influence damping as previously suggested. Future studies should focus on the subject-specific composition of soft-tissue compartments to elucidate their contribution to vibrations.

In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.

The purpose of this study was to determine the degree of co-contraction as per electromyographic gamma-band intermuscular coherence of the quadricep (Q) and hamstring (H) muscles during single-leg squatting (SLS), and to assess the influence of sex and self-reported knee complaints on the association between knee injury history and medial and lateral Q-H intermuscular coherence. Participants included 34 individuals who suffered a youth sport-related intra-articular knee injury 3–12 years previously, and 37 individuals with no knee injury history. Surface electromyographic signals were recorded from medial and lateral thigh muscles bilaterally to determine the gamma-band (30–60 Hz) intermuscular coherence between medial and lateral Q-H muscle pairs during SLS. Multivariable linear regression (α = 0.05) was performed to investigate the relationship between knee injury history (main exposure) and medial and lateral Q-H coherence (outcome) while accounting for the influence of sex and self-reported knee pain and symptoms (covariates). The median age of participants was 25 (range 18–30) and 67% were female. Q-H gamma-band coherence was present for 60–90% of legs. Medial and lateral Q-H coherence was higher in females compared to males. There was no evidence for an association between medial Q-H coherence, knee injury history, knee pain, or symptoms. There was evidence for an association between knee injury history and lateral Q-H coherence, which was modified by sex such that previously injured males demonstrated reduced Q-H coherence compared to uninjured males. These finding suggest that females demonstrate a more pronounced Q-H co-contraction strategy during a SLS than males regardless of knee injury history. Further, that male who suffered a youth sport-related knee injury 3–12 years previously demonstrate less Q-H co-contraction during a SLS than uninjured males. The mechanisms behind differences in neuromuscular control between males and females as well as previously injured and uninjured males require further investigation.

Boron neutron capture therapy (BNCT) is a targeted therapy, which consists of preferential accumulation of boron carriers in tumor followed by neutron irradiation. Each oral cancer patient has different risks of developing one or more carcinomas and/or oral mucositis induced after treatment. Our group proposed the hamster oral cancer model to study the efficacy of BNCT and associated mucositis. Translational studies are essential to the advancement of novel boron delivery agents and targeted strategies. Herein, we review our work in the hamster model in which we studied BNCT induced mucositis using three different cancerization protocols, mimicking three different clinical scenarios. The BNCT-induced mucositis increases with the aggressiveness of the carcinogenesis protocol employed, suggesting that the study of different oral cancer patient scenarios would help to develop personalized therapies.

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group (“group-level edges”) and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders.

OBJECTIVE This study examined the differential relationship of externalizing behavior, internalizing behavior, social context, and their interactions to three developmental indicators of smoking involvement: onset (age), amount of smoking, and dependence symptomatology. METHOD Participants (n = 504, 73% male) from a high-risk community-based longitudinal study were followed from age 12-14 to young adulthood (18-20). Smoking involvement was conceptualized as a process involving differences in (a) age of onset of smoking, (b) amount of smoking at age 18-20, and (c) level of nicotine dependence symptomatology at age 18-20. Survival analysis was used to predict onset of smoking, regression for smoking level, and zero-inflated Poisson regression for nicotine dependence. RESULTS Externalizing (teacher report) and internalizing behavior (youth self-report), prior to the onset of smoking, predicted different components of smoking and nicotine dependence in young adulthood. Parental smoking predicted all levels of smoking involvement. Peer smoking was related to early onset of smoking, but not higher levels of smoking involvement. Externalizing and internalizing behavior interacted to predict nicotine dependence level, with higher levels of internalizing behavior predicting higher levels of dependence symptoms, even at low levels of externalizing behavior. CONCLUSIONS Externalizing and internalizing behavior and social context are independent and interacting risk factors that come into play at different points in the developmental process occurring between smoking onset and dependence. This study provides important information for theoretical models of smoking progression and shows that different types of risk should be targeted for prevention at different points in smoking progression. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

One method to determine the forces produced during running is to conduct extensive kinematic and kinetic analysis. These analyses can be performed by having an individual perform repeated over-ground running trials or simply run continuously on an instrumented treadmill. The forces produced during over-ground running may not be the same as the forces during treadmill running and these differences could be attributed to a number of factors, including the design of the instrumented treadmill. The purpose of this paper was to determine whether there are differences in force measurements on different instrumented treadmill setups in comparison to over-ground running and to correct for any of these differences using a theoretical model. 11 participants ran on three different treadmills and performed over-ground running at 2.7, 3.6, and 4.5 m/s. Ground reaction forces were measured via force plates and an instrumented pressure insole. We found that the magnitude of the vertical ground reaction force differed between the three treadmills and over-ground running. The difference in ground reaction forces estimated by the pressure insole and the treadmill-force-plate system or instrumented treadmill can be explained by a three degree of freedom mechanical model of a person running on a treadmill and this model could potentially be used to correct for errors in force measurement from instrumented treadmills. The model included a force plate, a treadmill, and a wobbling mass with varying natural frequencies and damping characteristics, and constant masses. These findings provide researchers a method to correct forces from an instrumented treadmill set-up to determine a close approximation of the actual forces experienced by a participant during treadmill running.

Human gait is as unique to an individual as is their fingerprint. It remains unknown, however, what gait characteristics differentiate well between individuals that could define the uniqueness of human gait. The purpose of this work was to determine the gait characteristics that were most relevant for a neural network to identify individuals based on their running patterns. An artificial neural network was trained to recognize kinetic and kinematic movement trajectories of overground running from 50 healthy novice runners (males and females). Using layer-wise relevance propagation, the contribution of each variable to the classification result of the neural network was determined. It was found that gait characteristics of the coronal and transverse plane as well as medio-lateral ground reaction forces provided more information for subject identification than gait characteristics of the sagittal plane and ground reaction forces in vertical or anterior-posterior direction. Additionally, gait characteristics during the early stance were more relevant for gait recognition than those of the mid and late stance phase. It was concluded that the uniqueness of human gait is predominantly encoded in movements of the coronal and transverse plane during early stance.

Background Worldwide, scientific congresses are cancelled because of the COVID-19 pandemic. Yet, scientific exchange is more important than ever, especially for infectious diseases and infection prevention specialists. Within a prospective cohort of congress attendees, we evaluated the safety concept of the 2020 congress of the Swiss Societies of Infectious Diseases and Hospital Hygiene. Methods The congress was held between September 2nd and 4th 2020 in Geneva (Switzerland), where COVID-19 incidence in the week during the congress was 65 cases /100 000 population within 7 days. A rigorous safety concept was implemented including universal face masking, physical distancing during sessions, and maximal reduction of social events. We invited congress attendees to participate in this prospective cohort and used an anonymized online questionnaire to assess risk perception, risk exposures, symptoms and diagnosis of SARS-CoV-2 of attendees before, during and after the congress. Dried blood spots were taken from attendees on-site and four weeks later to detect specific antibodies against SARS-CoV-2 and to document seroconversions. Results A total of 365 people attended the congress, thereof 271 healthcare professionals. Of these, 196 (54%) either answered the questionnaire (N = 150) or provided baseline and follow-up blood samples (N = 168). None of the study participants reported a positive PCR result in the 2 weeks after the congress. Five of 168 (3%) participants were seropositive at follow-up, all of which had already been positive at baseline. The safety concept was deemed appropriate by 92% of the study participants and hygiene measures were performed correctly by the vast majority. Conclusion In this prospective cohort of congress attendees, no PCR positive cases or seroconversions could be documented after attending an on-site medical congress. These findings indicate that congresses with a rigorous safety concept may take place, even in areas with moderately-high COVID-19 activity.

Background Persons with multiple sclerosis (PwMS) often have reduced aerobic capacity and report fatigue as the most disabling symptom impacting their health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for successful management of symptoms, although there is little supporting evidence. The aim of this study is to evaluate the effect of a multimodal therapy approach, including endurance training and patient education, during a three-week inpatient rehabilitation stay, on HRQoL in PwMS at six months follow-up. Inpatient energy management education (IEME) + high-intensity interval training (HIIT) will be compared with progressive muscle relaxation (PMR) + moderate continuous training (MCT). Methods This study has a two-armed single-blind randomized controlled superiority trial design. One hundred six PwMS-related fatigue (relapsing-remitting or chronic progressive phenotypes; Expanded Disability Status Scale (EDSS) ≤ 6.5) will be recruited at the Valens clinic, Switzerland, and randomized into either an experimental (EG) or a control group (CG). EG: participants will perform IEME twice and HIIT three times per week during the three-week rehabilitation stay. IEME is a group-based intervention, lasting for 6.5 h over three weeks. HIIT contains of five 1.5-min high-intensive exercise bouts on a cycle ergometer at 95–100% of peak heart rate (HRpeak), followed by active breaks of unloaded pedalling for 2 min to achieve 60% of HRpeak. CG: participants will perform PMR twice and MCT three times per week during the three-week rehabilitation stay, representing local usual care. PMR consists of six 1-h relaxation group sessions. MCT consists of 24-min continuous cycling at 65% of HRpeak. The primary outcome is HRQoL (Physical and Mental Component Summaries of the Medical Outcome Study 36-item Short Form Health Survey; SF-36), measured at entry to the clinic (baseline, T0), three weeks after T0 (T1) and at four (T2) and six (T3) months after T0. Secondary outcomes comprise cardiorespiratory fitness, inflammatory markers (measured at T0 and T1), fatigue, mood, self-efficacy, occupational performance, physical activity (measured at T0, T1, T2 and T3) and behaviour changes in energy management (measured at T2 and T3). Discussion This study will provide detailed information on a multimodal therapy approach to further improve rehabilitation for PwMS. Trial registration This trial was prospectively registered at ClinicalTrials.gov (NCT04356248; 22 April 2020).

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 ( n = 145 ), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, n = 191 , and healthcare workers, n = 1002 ). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein–Barr virus (EBV) ( n = 9 ), cytomegalovirus (CMV) ( n = 7 ), and endemic common-cold coronavirus infections ( n = 12 ) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

Objective: To determine the effect of an innovative, online-based intervention, addressing the possible decline of physical activity (PA) and increase of sedentary behavior (SB) during COVID-19 stay at home restrictions in Switzerland. Methods: This study investigated the effect of a two-week, social cognitive theory based, online-video moderate to vigorous (MV)PA or SB intervention on MVPA and SB behaviour and intention via a 3 group by 2 time point parallel randomized controlled trial during the COVID-19 pandemic. Adults (≥18 yo) were recruited over the internet between April 10th and April 19th 2020 (n = 129; 75.2% female; mean age = 29.0 [SD 11.8] years). Both intervention groups received five videos targeting either SB for the SB group or MVPA for the MVPA group and were compared to an attention control group (fruit and vegetable consumption). It was hypothesized that MVPA time and intention would increase for the MVPA group and the SB group would outperform control on SB behaviour and intention indicators. Results: No significant interactions were found for the MVPA group (n = 41) versus control (n = 40). Only one significant interaction was measured for the SB group (n = 48; intention of active breaks F = (2,114) = 5.84, p = 0.004, ηp2 = 0.09). Although mostly non-significant and small effects, the MVPA group showed results pointing in the hypothesized direction on all PA indicators and the SB on all SB indicators, respectively. Conclusion: Considering this study’s limitations (e.g. small intervention dose), video-based online PA and SB interventions seem promising and feasible. This approach is appropriate for COVID-19 and other stay at home situations.

BACKGROUND The emergence and spread of multidrug-resistant organisms (MDRO) present a threat to human and animal health. OBJECTIVES To assess acquisition, prevalence of and risk factors for MDRO carriage in dogs and cats presented to veterinary clinics or practices in Switzerland. ANIMALS Privately owned dogs (n = 183) and cats (n = 88) presented to 4 veterinary hospitals and 1 practice. METHODS Prospective, longitudinal, observational study. Oronasal and rectal swabs were collected at presentation and 69% of animals were sampled again at discharge. Methicillin-resistant (MR) staphylococci and macrococci, cephalosporinase-, and carbapenemase-producing (CP) Enterobacterales were isolated. Genetic relatedness of isolates was assessed by repetitive sequence-based polymerase chain reaction and multilocus sequence typing. Risk factors for MDRO acquisition and carriage were analyzed based on questionnaire-derived and hospitalization data. RESULTS Admission prevalence of MDRO carriage in pets was 15.5% (95% confidence interval [CI], 11.4-20.4). The discharge prevalence and acquisition rates were 32.1% (95% CI, 25.5-39.3) and 28.3% (95% CI, 22-35.4), respectively. Predominant hospital-acquired isolates were extended spectrum β-lactamase-producing Escherichia coli (ESBL-E coli; 17.3%) and β-lactamase-producing Klebsiella pneumoniae (13.7%). At 1 institution, a cluster of 24 highly genetically related CP (blaoxa181 and blaoxa48 ) was identified. Multivariate analysis identified hospitalization at clinic 1 (odds ratio [OR], 5.1; 95% CI, 1.6-16.8) and days of hospitalization (OR 3-5 days, 4.4; 95% CI, 1.8-10.9; OR > 5 days, 6.2; 95% CI, 1.3-28.8) as risk factors for MDRO acquisition in dogs. CONCLUSIONS Veterinary hospitals play an important role in the selection and transmission of MDRO among veterinary patients.

Footwear comfort is an important factor in design, purchase and use of running shoes but current measures require multiple subjective assessments. Therefore, an objective and more reliable surrogate measure of footwear comfort would be of high relevance. In other research fields, perceived comfort was found to influence the variability of movement execution. Consequently, the purpose of this study was to investigate the influence of perceived footwear comfort on the variability of running kinematics as a potential surrogate measure of comfort. Thirty-six recreational athletes ran in five different running shoes on an indoor track while their running kinematics were recorded using a foot-mounted tri-axial inertial measurement unit (IMU). Footwear comfort was measured through multiple subjective assessments. The relative variability of IMU data was determined across the swing phase of 45 gait cycles and compared between the most and least comfortable shoes. Lower footwear comfort was associated with lower k...

Background Healthy internet activity (eg, making use of eHealth and online therapy) is positively associated with well-being. However, unhealthy internet activity (too much online time, problematic internet use/PIU, internet dependency/ID, etc.) is associated with reduced well-being, loneliness, and other related negative aspects. While most of the evidence is correlational, some research also shows that internet activity can be predictive for well-being. Objective The aim of this article is to elaborate on the question as to what extent internet activity is predictive of psychological well-being by means of (a) a scoping review and (b) theoretical understanding which model the interrelation of internet activity and psychological well-being. Methodology We searched different electronic databases such as Web of Science by using the search terms "Internet" OR "App" OR "digital" OR "online" OR "mobile application" AND "Use" OR "Activity" OR "Behavior" OR "Engagement" AND "Well-being" OR "Loneliness" for (a, the scoping review) or CCAM for (b, the theoretical understanding). Results The scoping review (a) summarizes recent findings: the extent to which internet activity is predictive for well-being depends on the internet activity itself: internet activity facilitating self-management is beneficial for well-being but too much internet activity, PIU and ID are detrimental to well-being. To understand (b) why, when and how internet activity is predictive for well-being, theoretical understanding and a model are required. While theories on either well-being or internet activity exist, not many theories take both aspects into account while also considering other behaviors. One such theory is the Compensatory Carry-Over Action Model (CCAM) which describes mechanisms on how internet use is related to other lifestyle behaviors and well-being, and that individuals are driven by the goal to adopt and maintain well-being - also called higher-level goals - in the CCAM. There are few studies testing the CCAM or selected aspects of it which include internet activity and well-being. Results demonstrate the potentials of such a multifactorial, sophisticated approach: it can help to improve health promotion in times of demographic change and in situations of lacking personnel resources in health care systems. Conclusion and recommendation Suggestions for future research are to employ theoretical approaches like the CCAM and testing intervention effects, as well as supporting individuals in different settings. The main aim should be to perform healthy internet activities to support well-being, and to prevent unhealthy internet activity. Behavior management and learning should accordingly aim at preventing problematic internet use and internet dependency.

PURPOSE OF REVIEW: Evidence is growing for the positive effects of technology-delivered diabetes self-care interventions on behavioral and clinical outcomes. However, our understanding of how to effectively implement these interventions into routine clinical practice is limited. This article provides an overview of the methods and results of studies examining the implementation of technology-delivered diabetes self-care interventions into clinical care. We focus specifically on patient-facing behavioral interventions delivered with technology (e.g., text messaging, apps, websites). RECENT FINDINGS: Eleven articles were included in the review. Most studies (n=9) examined barriers and facilitators to implementation, while about half (n=5) integrated the intervention into clinical care and evaluated implementation and/or effectiveness. Only six studies applied a theory or framework. The most common determinants of implementation were time constraints for clinic staff, familiarity with technology, knowledge of the intervention, and perceived value. We found substantial variation in implementation outcomes, including which were reported, how they were assessed, and the results. In the four studies that evaluated effectiveness, hemoglobin A1c improved. SUMMARY: Successful implementation of technology-delivered interventions has the potential to transform healthcare delivery and improve diabetes health on a population level. Promising strategies to address common determinants of implementation include appointing a clinic champion, developing staff training and educational materials, and adapting intervention processes to the clinic context. Future research should evaluate these implementation strategies to understand when and how they impact outcomes. Frameworks such as Reach Effectiveness Adoption Implementation Maintenance (RE-AIM), can help ensure outcomes are systematically reported and allow for comparison across studies.

Background Intensive medical care in companion animal clinics could pose a risk for the selection and dissemination of multidrug-resistant organisms (MDROs). Infection prevention and control (IPC) concepts are key measures to reduce the spread of MDROs, but data on IPC standards in companion animal clinics is sparse. The study assessed IPC standards in seven companion animal clinics and practices in Switzerland by structured IPC audits and combined results with environmental MDRO contamination and MDRO carriage of the personnel. Methods IPC audits were held between August 2018 and January 2019. The observations in 34 IPC areas were scored based on predefined criteria (not fulfilled/partially fulfilled/fulfilled = score 0/1/2). Environmental swabs and nasal and stool samples from veterinary personnel were tested for methicillin-resistant (MR) staphylococci and macrococci and for colistin-resistant, extended-spectrum β-lactamase- and carbapenemase-producing (CP) Enterobacterales (CPE). Species was identified by MALDI-TOF MS, antimicrobial resistance determined by microdilution and β-lactam resistance gene detection, and genetic relatedness assessed by REP−/ERIC-PCR and multilocus sequence typing. Results Of a maximum total IPC score of 68, the institutions reached a median (range) score of 33 (19–55). MDROs were detected in median (range) 8.2% (0–33.3%) of the sampling sites. Clinics with low IPC standards showed extensive environmental contamination, i.e. of intensive care units, consultation rooms and utensils. CPE were detected in two clinics; one of them showed extensive contamination with CP Klebsiella pneumoniae (ST11, blaOXA-48) and MR Staphylococcus pseudintermedius (ST551, mecA). Despite low IPC scores, environmental contamination with MDROs was low in primary opinion practices. Three employees were colonized with Escherichia coli ST131 (blaCTX-M-15, blaCTX-M-27, blaCTX-M-14). Two employees carried CP E. coli closely related to environmental (ST410, blaOXA-181) and patient-derived isolates (ST167, blaNDM-5). MR Staphylococcus aureus (ST225, mecA) and MR S. pseudintermedius (ST551, mecA) of the same sequence types and with similar resistance profiles were found in employees and the environment in two clinics. Conclusions The study indicates that IPC standards in companion animal clinics are variable and that insufficient IPC standards could contribute to the evolution of MDROs which can be transferred between the environment and working personnel. The implementation of IPC concepts in companion animal clinics should urgently be promoted.

Early life predictors of attention-deficit/hyperactivity disorder (ADHD) are critically needed; they could inform etiological theory and may help identify new prevention targets. The current study examined prospectively whether maternal cytokine levels during pregnancy predict offspring ADHD symptoms at age 4–6 years. Secondarily, we evaluated maternal cytokine levels as a possible common pathway through which prenatal risks exert influence on child ADHD. Data came from a sample of women recruited during the 2nd trimester of pregnancy (N = 62) and followed postnatally until children were 4–6 years old. Maternal inflammation was assessed using 3rd trimester plasma concentrations of three indicators of nuclear factor kappa B signaling: interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 which were combined into a latent variable. Mothers and teachers reported on child ADHD symptoms, negative affect, and externalizing behaviors at 48–72 months of age. Maternal inflammation in the 3rd trimester predicted ADHD symptoms when children were 4–6 years old (β = 0.53, 95% CI = 0.154, 0.905, p = 0.006). Further, maternal inflammation mediated the effect of prenatal distress on child ADHD (β = 0.21, 95% CI = 0.007, 0.419, p = 0.04). The inflammation effect on ADHD was not explained by concurrent child negative affect, externalizing behavior, or familial ADHD status. This is the first human study to prospectively link maternal pregnancy cytokine levels and offspring ADHD symptoms, suggesting that cytokine levels are a possible marker of ADHD risk. Results also provide new evidence that maternal prenatal inflammation may be one common pathway by which prenatal risk factors influence offspring mental health outcomes.

Studies on the paradigm of the preferred movement path are scarce, and as a result, many aspects of the paradigm remain elusive. It remains unknown, for instance, how muscle activity adapts when differences in joint kinematics, due to altered running conditions, are of low / high magnitudes. Therefore, the purpose of this work was to investigate changes in muscle activity of the lower extremities in runners with minimal (≤ 3°) or substantial (> 3°) mean absolute differences in the ankle and knee joint angle trajectories when subjected to different running footwear. Mean absolute differences in the integral of the muscle activity were quantified for the tibialis anterior (TA), peroneus longus (PL), gastrocnemius medialis (GM), soleus (SO), vastus lateralis (VL), and biceps femoris (BF) muscles during over ground running. In runners with minimal changes in 3D joint angle trajectories (≤ 3°), muscle activity was found to change drastically when comparing barefoot to shod running (TA: 35%; PL: 11%; GM: 17%; SO: 10%; VL: 27%; BF: 16%), and minimally when comparing shod to shod running (TA: 10%; PL: 9%; GM: 13%; SO: 8%; VL: 8%; BF: 12%). For runners who showed substantial changes in joint angle trajectories (> 3°), muscle activity changed drastically in barefoot to shod comparisons (TA: 39%; PL: 14%; GM: 16%; SO: 16%; VL: 25%; BF: 24%). It was concluded that a movement path can be maintained with small adaptations in muscle activation when running conditions are similar, while large adaptations in muscle activation are needed when running conditions are substantially different.

Objective(s) The hamster carcinogenesis model recapitulates oral oncogenesis. Dimethylbenz[a]anthracene (DMBA) cancerization induces early severe mucositis, affecting animal's welfare and causing tissue loss and pouch shortening. "Short" pouches cannot be everted for local irradiation for boron neutron capture therapy (BNCT). Our aim was to optimize the DMBA classical cancerization protocol to avoid severe mucositis, without affecting tumor development. We evaluated BNCT in animals cancerized with this novel protocol. Materials and methods We studied: Classical cancerization protocol (24 applications) and Classical with two interruptions (completed at the end of the cancerization protocol). BNCT mediated by boronophenylalanine (BPA) was performed in both groups. Results The twice-interrupted group exhibited a significantly lower percentage of animals with severe mucositis versus the non-interrupted group (17% versus 71%) and a significantly higher incidence of long pouches (100% versus 53%). Tumor development and the histologic characteristics of tumor and precancerous tissue were not affected by the interruptions. For both groups, overall tumor response was more than 80%, with a similar incidence of BNCT-induced severe mucositis. Conclusion(s) The twice-interrupted protocol reduced severe mucositis during cancerization without affecting tumor development. This favored the animal's welfare and reduced the number of animals to be cancerized for our studies, without affecting BNCT response.

Despite the frequent use of the electromyography-based muscle co-contraction index (CCI) to examine muscular control of the knee joint in young adults with and without knee injury history, the reliability of the CCI in this population is unknown. The purpose of this study was to quantify within-day and between-day reliability of the knee muscle CCI during gait in young adults with and without knee injury history. Twenty young adults (10 males, 10 females) with and without history of intra-articular knee injury performed repeated gait analyses on two different days. Surface electromyography of periarticular knee muscles was performed to determine CCIs for medial and lateral knee extensor – flexor pairs. Absolute (Bland-Altman ratio limits of agreement) and relative (ICCs) reliability were determined between two sessions on the same day as well as on different days. Within-day reliability was good to excellent for most analyzed co-contraction outcomes (ICCs > 0.9) and was deemed acceptable in the context of clinically relevant changes in co-contraction in response to interventions. Between two separate days, the CCI showed poor reliability with measurement errors of up to 300% and was consequently not recommended as a tool to monitor long-term changes or group differences in knee muscular control.

Background and objectives Patients with isolated colorectal-cancer-liver-metastases (CRCLM) frequently undergo metastatectomy. Tumor-infiltrating-lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor-infiltrating CD8+ cytotoxic T-cells and FoxP3+ regulatory T-cells at the metastatic site of CRCLM patients. Methods TILs were isolated from fresh metastatic tissues of 47 patients with CRCLM. Archived paraffin-embedded tissue, from the same patients, was retrieved. CD8+ and FoxP3+ cells, both in the intra-tumoral and the peri-tumoral compartments, were measured by immunohistochemistry on full tissue sections. Proportions of cytotoxic T-cells (CD8+ ) and regulatory T-cells (CD4+ CD25+ FoxP3+ ), within CD45+ TILs, were measured by flow-cytometry. Results By immunohistochemistry, individual densities of intra-tumoral or peri-tumoral CD8+ and FoxP3+ cells were not prognostic of survival. However, the intra-tumoral, but not the peri-tumoral, CD8+ /FoxP3+ ratio was an independent predictor of survival (HR 0.43, 95%CI 0.19-0.95, P = 0.032). By flow cytometry, the intra-tumoral CD8+ /regulatory T-cell ratio was also an independent predictor of survival (HR 0.45, 95%CI 0.20-0.99, P = 0.044). Conclusions The ratio of cytotoxic (CD8+ ) to regulatory (FoxP3+ ) T-cells, in the intra-tumoral compartment, but not in the peri-tumoral compartment, can predict survival after resection of CRCLM.

The repetitive loads placed on the Achilles tendon (AT) during running are associated with microdamage accumulation, which has been proposed as a precursor to Achilles tendinopathy. The rate of mic...

Reviewer acknowledgement for the years 2019 and 2020.

BACKGROUND: Patients with Parkinson's disease exhibit disturbed manual dexterity. This impairment leads to difficulties in activities of daily living, such as buttoning a shirt or hand-writing. The aim of the present study was to investigate the effectiveness of a home-based dexterity program on fine motor skills in a single-blinded, randomized controlled trial, in patients with Parkinson's disease.METHODS: One hundred and three patients with Parkinson's disease (aged between 48 and 80 years, Hoehn & Yahr stage I-IV) were randomized to either a home-based dexterity program (HOMEDEXT) or Thera-band program. All patients trained over a period of 4 weeks, 5 times/week, 30 min for each session. A baseline, post-intervention, and follow-up assessment (12 weeks later, time period without intervention) were done. The primary outcome measure was dexterity as measured with the Nine Hole peg test (9-HPT). Secondary outcome measures included strength, motor parkinsonian symptoms, dexterity-related activities of daily living (ADL) and Health-related Quality of Life (HrQoL).RESULTS: There was a significant difference in favor of the HOMEDEXT group as compared to the Thera-band group on the primary outcome 9-HPT (p = 0.006) and dexterity-related ADL (p = 0.02) at post intervention. No significant differences were found for the other outcomes, nor at follow-up.CONCLUSION: This is the first randomized controlled trial showing that an intensive, task specific home-based dexterity program significantly improved fine motor skills in Parkinson's disease. The effect generalized to dexterity-related ADL functions. As these improvements did not sustain, the finding suggest that continuous training is required to maintain the benefit.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9)-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.